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A blood sample drawn from a vein in your arm

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The Test Sample

What is being tested?

A hemoglobinopathy is an inherited blood disorder in which an individual has an abnormal form of hemoglobin (variant) or decreased production of hemoglobin (thalassemia). A hemoglobinopathy evaluation is a group of tests that identifies abnormal forms of or suggests problems with production of hemoglobin in order to screen for and/or diagnose a hemoglobin disorder.

Hemoglobin (Hb) is the iron-containing protein found in all red blood cells (RBCs) that binds to oxygen in the lungs and allows RBCs to carry the oxygen throughout the body, delivering it to the body's cells and tissues. Hemoglobin consists of one portion called heme, which is the molecule with iron at the center, and another portion made up of four globin (protein) chains. The globin chains, depending on their structure, have different designations: alpha, beta, gamma, and delta. The types of globin chains that are present are important in the function of hemoglobin and its ability to transport oxygen.

Normal hemoglobin types include:

Hemoglobin A: makes up about 95%-98% of Hb found in adults; it contains two alpha and two beta protein chains.

Hemoglobin A2: makes up about 2%-3% of Hb in adults; it has two alpha and two delta protein chains.

Hemoglobin F (fetal hemoglobin): makes up to 1%-2% of Hb found in adults; it has two alpha and two gamma protein chains. This is the primary hemoglobin produced by the fetus during pregnancy; its production usually falls shortly after birth and reaches adult levels by 1-2 years.

Hemoglobinopathies occur when changes (mutations) in the genes that code for the globin chains cause alterations in the proteins. These genetic changes may result in a reduced production of one of the normal globin chains or in the production of structurally altered globin chains. Genetic mutations may affect the structure of the hemoglobin, its behavior, its production rate, and/or its stability. The presence of abnormal hemoglobin within RBCs can alter the appearance (size and shape) and function of the red blood cells.

Red blood cells containing abnormal hemoglobin (hemoglobin variants) may not carry oxygen efficiently and may be broken down by the body sooner than usual (a shortened survival), resulting in hemolytic anemia. Some of the most common hemoglobin variants include hemoglobin S, the primary hemoglobin in people with sickle cell disease that causes the RBC to become misshapen (sickle), decreasing the cell's survival; hemoglobin C, which can cause a minor amount of hemolytic anemia; and hemoglobin E, which may cause no symptoms or generally mild symptoms.

Thalassemia is a condition in which a gene mutation results in reduced production of one of the globin chains. This can upset the balance of alpha to beta chains, causing abnormal hemoglobin to form (alpha thalassemia) or causing an increase of minor hemoglobin components, such as Hb A2 or Hb F (beta thalassemia).

Many other less common hemoglobin variants exist. Some are silent – causing no signs or symptoms – while others affect the function and/or stability of the hemoglobin molecule. An investigation of a hemoglobin disorder typically involves tests that determine the types and amounts of hemoglobin present in a person's sample of blood. Some examples include:

Hemoglobin solubility test: used to test specifically for hemoglobin S, the main hemoglobin in sickle cell disease

Is any test preparation needed to ensure the quality of the sample?

The Test

How is it used?

A hemoglobinopathy evaluation is used to detect abnormal forms and/or relative amounts of hemoglobin, the protein found in all red blood cells that transports oxygen. Testing may be used for:

Screening

All states require that newborns be screened for certain hemoglobin variants.

Prenatal screening is often performed on high-risk parents with an ethnic background associated with a higher prevalence of hemoglobin abnormality and those with affected family members. Screening may also be done in conjunction with genetic counseling prior to pregnancy to determine whether the parents are carriers.

To identify variants in asymptomatic parents who have an affected child

Several different laboratory methods are available to evaluate the types of hemoglobin that a person has. Some of these include:

Hemoglobin solubility test: used to test specifically for hemoglobin S, the main hemoglobin in sickle cell disease

Hemoglobin electrophoresis (Hb ELP)

Hemoglobin isoelectric focusing (Hb IEF)

Hemoglobin by high performance liquid chromatography (HPLC)

These methods evaluate the different types of hemoglobin based on the physical and chemical properties of the different hemoglobin molecules.

Most of the common hemoglobin variants or thalassemias can be identified using one of these tests or a combination. The relative amounts of any variant hemoglobin detected can aid in a diagnosis. However, a single test is usually not sufficient to establish a diagnosis of hemoglobinopathy. Rather, the results of several different tests are considered. Examples of other laboratory tests that may be performed include:

Genetic testing: may be used to detect mutations in the genes that code for the protein chains (alpha and beta globulin) that comprise hemoglobin. This is not a routine test but can be used to confirm whether a person has a mutated gene and whether there is one or two mutated copies (heterozygous or homozygous).

It may be ordered when a doctor suspects that a person's signs and symptoms are the result of abnormal hemoglobin production. Abnormal forms of hemoglobin often lead to hemolytic anemia, resulting in signs and symptoms such as:

Some severe forms of hemoglobinopathies (e.g., sickle cell disease) may result in serious signs and symptoms, such as episodes of severe pain, shortness of breath, enlarged spleen, and growth problems in children.

What does the test result mean?

Care must be taken when interpreting the results of a hemoglobinopathy evaluation. Typically, the laboratory report includes an interpretation by a pathologist with experience in the field of hematology (hematopathologist).

Results of the evaluation usually report the types of hemoglobin present and the relative amounts. For adults, percentages of normal hemoglobins include:

Hemoglobin A1(HB A1): about 95%-98%

Hemoglobin A2 (Hb A2): about 2%-3%

Hemoglobin F (Hb F): 2% or less

Testing may help diagnose a condition that causes the production of structurally altered hemoglobin (variant) or a condition called thalassemia, in which a genemutation results in reduced production of one of the globin chains. This can upset the balance of alpha to beta chains, causing abnormal hemoglobin to form (alpha thalassemia) or causing an increase of minor hemoglobin components, such as Hb A2 or Hb F (beta thalassemia).

Some of the most common abnormal forms of hemoglobin that may be detected and measured with this testing include:

Hemoglobin S (Hb S): this is the primary hemoglobin in people with sickle cell disease. About 1 in 500 African American babies are born with this disorder, and more than 70,000 Americans are living with the disease, according to the Centers for Disease Control and Prevention. Individuals with sickle cell disease (two copies of the abnormal gene) have a high percentage of Hb S. People with sickle cell trait have a moderate amount of Hb S (about 40%) but still have the normal form of Hb A (about 60%). Hb S causes the red blood cell to become misshapen (sickle) when exposed to a low level of oxygen (such as might happen when someone exercises or has infection in the lungs). Sickled red blood cells can block small blood vessels, causing pain, impaired circulation, and decreased oxygen delivery to tissues and cells, and decrease the cell's survival. High amounts of hemoglobin A or F can keep enough oxygen in the red blood cells to prevent sickling from occurring.

Hemoglobin C (Hb C): about 2-3% of people of African descent have hemoglobin C trait (one copy of the gene for Hb C). Hemoglobin C disease (seen in those with two copies of the gene) is rare and relatively mild. It usually causes a minor amount of hemolytic anemia and a mild to moderate enlargement of the spleen.

Hemoglobin E (Hb E): this is one of the most common beta chain hemoglobin variants in the world. It is very prevalent in individuals of Southeast Asian descent. People who are homozygous for Hb E generally have a mild hemolytic anemia, microcytic red blood cells, and a mild enlargement of the spleen. A single copy of the hemoglobin E gene does not cause symptoms unless it is combined with another mutation (e.g., a mutation causing beta thalassemia).

Some less common forms include:

Hemoglobin F (Hb F): this is the primary hemoglobin produced by a developing fetus. Normally, production of Hb F drops significantly after birth and decreases to adult levels by 1-2 years of age. Hb F may be elevated in several disorders, such as beta thalassemia and sickle cell anemia.

Hemoglobin H (Hb H): occurs in some cases of alpha thalassemia. It is composed of four beta globin chains and is produced due to a severe shortage of alpha chains. Although each of the beta globin chains is normal, the four beta chains do not function normally.

Hemoglobin Barts: this type develops in fetuses with alpha thalassemia. It is formed of four gamma protein chains when there is a shortage of alpha chains, in a manner similar to the formation of Hb H. Hb Barts disappears shortly after birth due to dwindling gamma chain production.

Other types that may be identified include:

Hemoglobin D

Hemoglobin G

Hemoglobin J

Hemoglobin M

Hemoglobin Constant Spring

A person can also inherit two different abnormal genes, one from each parent. This is known as being compound heterozygous or doubly heterozygous. Several different clinically significant combinations include hemoglobin SC disease, sickle cell – hemoglobin D disease, hemoglobin E – beta thalassemia, and hemoglobin S – beta thalassemia. For more on these, see the articles on Hemoglobin Abnormalities and Thalassemia.

Some examples of results that may be seen with a hemoglobinopathy evaluation are listed in the following table.

Is there anything else I should know?

Blood transfusions can interfere with hemoglobinopathy evaluation. A patient should wait several months after a transfusion before having this testing done. However, in people with sickle cell disease, the testing may be performed after a transfusion to determine if enough normal hemoglobin has been given to reduce the risk of damage from sickling of red blood cells.

Common Questions

1. Why is every newborn screened for hemoglobinopathies?

Newborn screening helps to identify potentially treatable or manageable congenital disorders within days of birth. Potentially life-threatening health problems and serious lifelong disabilities can be avoided or minimized if a condition is quickly identified and treated. Also, since newborn screening programs have mandated testing for hemoglobin variants, they have uncovered thousands of children who are carriers. (This is due to new technology, not to an increased prevalence of the gene mutations.) Information on carrier status may be important in their future if and when they begin to plan a family.

2. Does everyone with hemolytic anemia need this testing?

3. How long will it take to get results?

It depends on the method of testing and the laboratory performing the evaluation. This testing requires specialized equipment and not every laboratory performs this test. Your sample may be sent to a reference laboratory, so it may take several days before results are available.

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Article Sources

NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.

(September 16, 2011) Centers for Disease Control and Prevention. Sickle Cell Disease, Data and Statistics. Available online at http://www.cdc.gov/NCBDDD/sicklecell/data.html through http://www.cdc.gov. Accessed February 2013.

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This article was last reviewed on March 14, 2013. | This article was last modified on July 21, 2013.

The review date indicates when the article was last reviewed from beginning to end to ensure that it reflects the most current science. A review may not require any modifications to the article, so the two dates may not always agree.

The modified date indicates that one or more changes were made to the article. Such changes may or may not result from a full review of the article, so the two dates may not always agree.